RNA interference (RNAi) is a cellular mechanism by which 21-23 nucleotide RNA duplexes trigger the degradation of cognate mRNAs. Researchers have been pursuing potential therapeutic applications of RNAi once it was demonstrated that exogenous, short interfering RNAs (siRNAs) can silence gene expression via this pathway in mammalian cells. RNAi is attractive for therapeutics because of its stringent target gene specificity, the relatively low immunogenicity of siRNAs, and the simplicity of design and testing of siRNAs.
Double-stranded RNA (dsRNA) can induce sequence-specific posttranscriptional gene silencing in many organisms by a process known as RNA interference (RNAi). However, in mammalian cells, dsRNA that is 30 base pairs or longer can induce sequence-nonspecific responses that trigger a shut-down of protein synthesis. RNA fragments are the sequence-specific mediators of RNAi. Interference of gene expression by these RNA interference (RNAi) molecules is now recognized as a naturally occurring strategy for silencing genes in the cells of many organisms.
One technical hurdle for RNAi-based clinical applications that still remains is the delivery of siRNAs across the plasma membrane of cells in vivo. A number of solutions for this problem have been described. However, most of the approaches described to date have the disadvantage of delivering siRNAs to cells non-specifically, without regard to the cell type.
For in vivo use, the therapeutic siRNA reagents need to target particular cell types (e.g., cancer cells), thereby limiting side-effects that result from non-specific delivery as well as reducing the quantity of siRNA necessary for treatment.